Medication discovery for addiction: translating the dopamine D3 receptor hypothesis.
Medication discovery for addiction: translating the dopamine D3 receptor hypothesis.
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DOI：
10.1016/j.bcp.2012.06.023
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发表时间：
2012-10-01
影响因子：
5.8
通讯作者：
Skolnick, Phil
中科院分区：
文献类型：
--
作者：
Newman, Amy Hauck;Blaylock, Brandi L.;Nader, Michael A.;Bergman, Jack;Sibley, David R.;Skolnick, Phil
多巴胺 D3 受体 (D3R) 已被研究作为治疗药物滥用障碍 (SUD) 药物开发的潜在靶标，特别关注可卡因和甲基苯丙胺。目前，还没有批准的药物可以治疗可卡因和甲基苯丙胺成瘾，因此开发药物治疗方法来补充现有的行为策略是一个基本目标。具有高亲和力和 D3R 选择性的新型化合物已在许多药物滥用动物模型中进行了评估，并且在非人类灵长类动物的自我给药和复发模型中取得了良好的结果，为将这些药物推向临床提供了令人信服的证据。一种方法是重新利用具有 D3R 机制并已具有临床实用性的药物，为此，丁螺环酮已被确定为临床试验的可行候选药物。第二种但资源密集且风险更大的方法涉及开发专门针对 D3R 的化合物，例如 GSK598809 和 PG 619。对这些药物或其他新型 D3R 选择性药物的临床研究将有助于更好地了解 D3R 在成瘾中的作用，以及 D3R 选择性拮抗剂或部分激动剂是否能有效帮助该患者实现戒断。 人口。
The dopamine D3 receptor (D3R) has been investigated as a potential target for medication development to treat substance use disorders (SUDs) with a particular focus on cocaine and methamphetamine. Currently, there are no approved medications to treat cocaine and methamphetamine addiction and thus developing pharmacotherapeutics to compliment existing behavioral strategies is a fundamental goal. Novel compounds with high affinity and D3R selectivity have been evaluated in numerous animal models of drug abuse and favorable outcomes in nonhuman primate models of self-administration and relapse have provided compelling evidence to advance these agents into the clinic. One approach is to repurpose drugs that share the D3R mechanism and already have clinical utility, and to this end buspirone has been identified as a viable candidate for clinical trials. A second, but substantially more resource intensive and risky approach involves the development of compounds that exclusively target D3R, such as GSK598809 and PG 619. Clinical investigation of these drugs or other novel D3R-selective agents will provide a better understanding of the role D3R plays in addiction and whether or not antagonists or partial agonists that are D3R selective are effective in achieving abstinence in this patient population.
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作者：
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